Hepatitis B virus (HBV) has infected over 2 billion people worldwide. It causes a variety of disease conditions in humans ranging from mild subclinical infection to chronic active and fulminant hepatitis. Over 400 million people, especially children and the elderly, are chronically infected with HBV. Hepatitis B virus is 100 times more infectious than the AIDS virus, yet it can be prevented with vaccination. Thus, the focal point in combating HBV includes vaccination. A vaccine is of no use for those already infected with hepatitis B. If the virus is detected soon enough, however, treatment options are available for those chronically infected. Accordingly, diagnostic assays have focused on identifying target antigens of the HBV virus for sufficiently early detection.
The HBV genome is a circular, partially double-stranded DNA approximately 3200 base pairs in length, and encodes seven viral proteins. The HBV envelope consists of three glycosylated proteins (large, medium and small HBV surface proteins, or LHB, MHB, and SHB, respectively), which are encoded by the same gene, but are produced from three different initiation sites and share the same termination site. The three different regions of the envelope protein gene, preS1, preS2, and S, encode LHB, MHB, and SHB, respectively (See FIG. 1 and FIG. 2). These three proteins are expressed at different ratios and assemble to form the outer capsid of the HBV virion and also form an incomplete viral particle. HBV surface antigen assays detect both forms of expression products virions and particles.
Regions of the HBV proteins are exposed on HBV particle surfaces and may be the targets of immune surveillance. However, HBV exhibits a high mutation rate due to its essential reliance on reverse transcriptase (RT) in replication, and the poor proofreading ability of RT. Accordingly, HBV is capable of evading immune surveillance and vaccination regimens via mutations in the envelope proteins, including SHB. Furthermore, because some methods of HBV detection depend on monitoring epitopes within the envelope proteins by using anti-SHB antibodies, highly mutable HBV may also escape detection. There is hence a continued need in the art for methods and compositions for detecting HBV.